Fig. 2

FGFR signaling in cancers. FGF, HSPG, and FGFR form 2:2:2 ternary complex, followed by receptor dimerization and kinase transphosphorylation. FGFR downstream adaptor protein FRS2 interacts with SHP2 and GRB2 complex, leading to subsequent activation of PI3K-AKT and RAS-MEK-ERK signaling pathways. Another FGFR substrate, PLC-g, binds to phosphotyrosine and hydrolyzes PIP2 to generate IP3 and DAG, which in turn activate PKC and MAPK pathway, resulting in cell migration, proliferation, and differentiation. Depending on the cellular context, FGFRs have the capability to activate the JAK-STAT3 signalling pathway. Aberrant FGFR signaling may be induced by (i) increased expression of FGFs (ligand-dependent), or (ii) FGFR alteration, including mutation, amplification or translocation (ligand-independent)